Emerging Infectious Diseases

Clinical Case Studies

Onder Ergonul, Fusun Can, Murat Akova, Lawrence Madoff

• Publisher: Academic Press
• Year: 2014
• eBook ISBN: 9780124201095
• Topic: Biological Sciences
• Subtopic: Immunology
• Index: Biological Sciences

More than 30 newly emerged microorganisms and related diseases have been discovered in the past 20 years. Since these infections are so new, even infectious diseases experts and clinical microbiologists need more information. This book covers recently emerged infectious diseases based on real cases and provides comprehensive information including different aspects of the infections. Written in a 'teaching' style, this book is of interest to every medical specialist and student. - Includes more than 35 emerging infection cases based on the following criteria:newly emerged or re-emergedrecently acquired significance in clinical practicerecently radically changed in case management - Offers a balanced synthesis of basic and clinical sciences for each individual case, presenting clinical courses of the cases in parallel with the pathogenesis and detailed microbiological information for each infection - Describes the prevalence and incidence of the global issues and current therapeutic approaches - Presents the measures for infection control

Chapter 1

Severe Fever with Thrombocytopenia Syndrome Associated with a Novel Bunyavirus

Keita Matsuno, Heinz Feldmann and Hideki Ebihara, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly recognized pathogen and the first highly pathogenic tick-borne virus reported in the genus Phlebovirus, family Bunyaviridae. Except for some basic knowledge on viral biology and epidemiology as well as the establishment of diagnostics and the description of the clinical disease syndrome, little is known about this emerging pathogen. Currently, there are neither therapeutic approaches nor vaccines available for the treatment and prophylaxis of SFTSV infections. In the absence of more thorough ecology and epidemiology, prevention is based on education targeting towards avoiding exposure through ticks and blood and secretions/excretions of patients. Urgently needed are further studies on the pathogenesis and host responses to infection in order to define targets for therapeutic intervention and strategies for vaccination.

Keywords

severe fever with thrombocytopenia syndrome virus; SFTSV; phlebovirus; tick-borne disease; epidemiology; pathogenesis; diagnosis; disease control

Case Presentation

A 40-year-old female farmer, who lived in a rural, hilly area outside Chizhou city, in Anhui Province, China, was admitted to a hospital in Shanghai (400 km/78 miles from Chizhou) in the middle of May 2012. She had no other known underlying medical conditions but a history of schistosomiasis in 2008. There was no history of previous drug or food allergies or blood transfusions.

On May 16, 2012, the patient had sudden onset of fever with a peak temperature of 40°C accompanied by muscle pain. She was examined and subsequently admitted to a local hospital, where treatment with intravenous antibiotics was started. Following no improvement, the patient was transferred on May 19 to a hospital in Chizhou, where treatment was changed to aztreonam and ribavirin. With no changes in her clinical status and fever remaining high, the patient was transferred to a hospital in Shanghai on May 21, where she presented with continuing fever, chills, body aches, and diarrhea (five to six times a day). The suspected diagnosis of SFTS was made and the patient was admitted to the intensive care unit (ICU). Her treatment was continued with cefotiam, levodropropizine, and intensive care support. The condition of the patient deteriorated and she became apathetic on May 22. Subsequent treatment included vancomycin and platelet substitution therapy, but her condition further deteriorated. The following day she presented with a stiff neck, accompanied by enlarged lymph nodes in the neck, axillar and mediastinum, and abnormal brain waves on electroencephalogram. On May 25, the patient was in critical condition with shortness of breath, hypotension (88/50 mmHg), oliguria, severe acidosis, an abnormal flow index, but no skin bleeding or blood stasis. Thereafter, she was treated with prednisone, platelet and plasma transfusions, and hemodialysis before she died on the same day (May 25th) with multi-organ failure including kidney and lung, disseminated intravascular coagulation, and shock.

Laboratory findings showed decreased white blood cell counts throughout the disease progression, which increased on the day of her death. The platelet count (PLT) decreased over time along with concomitant prolonged thrombin time (TT) and activated partial thromboplastin time (APTT). Multi-organ dysfunction (including liver and kidney failure) was evident by elevated blood urea nitrogen (BUN) and hepatic transaminases (alanine aminotransferase, ALT; aspartate aminotransferase, AST), lactate dehydrogenase (LDH), and creatine kinase (CK). The presence of microscopic hematuria and proteinuria was also documented. On May 25 the results of an arterial blood gas were consistent with severe metabolic acidosis and respiratory compensation (pH: 7.17; PCO₂: 14.0 mmHg; PO₂: 110 mmHg; ${{\mathrm{HCO}}_3}^{-}$

: 5.10 mmol/L; ${{\mathrm{CO}}_2}^{-}\mathrm{Ct}$

: 5.5 mmol/L; Beecf: −23.4 mmol/L; SBC: 8.5; Beb: −21.1 mmol/L; SO₂: 97%).

SFTSV infection was confirmed by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) following death. The patient had no known exposure to tick bites, but contact history with birds, rodents, and other wild animals was reported. Her activities during the past 2 weeks prior to disease onset involved fieldwork collecting cotton, rice, and tea. She had no known exposure to an SFTSV case or a person with similar illness and no similar cases were found in and around her residence. No secondary SFTSV cases were found among her contacts (adapted from reference¹).

1 Why this Case was Significantly Important as an Emerging Infection

Severe fever with thrombocytopenia syndrome (SFTS) was discovered in 2009 in Central China as a newly emerged clinical syndrome with clinical and epidemiological similarity to human anaplasmosis.² The causative agent of SFTS was identified as a novel phlebovirus, SFTS virus (SFTSV). Currently, SFTS cases have been reported from China, Japan, and South Korea with case fatality rates ranging from 10 to 30%. A milder but similar disease has been reported from the United States caused by Heartland virus, which is a recently related discovered phlebovirus.³

2 What is the Causative Agent?

SFTSV is tentatively classified as a novel member of the genus Phlebovirus, family Bunyaviridae. As other bunyaviruses, SFTSV is an enveloped spherical-shaped particle, about 80–100 nm in diameter, carrying a genome of three segmented negative-stranded RNA molecules. The large RNA (L) segment is 6368 nucleosides in length and encodes for the RNA-dependent RNA polymerase (RdRp), which is responsible for viral RNA transcription and replication. The medium RNA (M) segment is 3378 nucleosides in length and encodes a membrane glycoprotein precursor, which is cleaved into the two mature membrane glycoproteins (Gn and Gc). Finally, the small RNA (S) segment is 1744 nucleosides in length encoding the nucleocapsid protein (N) and a non-structural protein (NSs) in an ambisense orientation (Figure 1.1).² Based on phylogenetic analysis of SFTSV isolates/sequences, the Chinese isolates currently form five distinct genetic lineages.⁴ The Japanese isolates mostly belong to lineage D, whereas the Korean isolate clusters belong to l...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• List of Contributors
• Preface
• Chapter 1. Severe Fever with Thrombocytopenia Syndrome Associated with a Novel Bunyavirus
• Chapter 2. Bas-Congo Virus: A Novel Rhabdovirus Associated with Acute Hemorrhagic Fever
• Chapter 3. Hantavirus Infections
• Chapter 4. Lassa Fever
• Chapter 5. Alkhurma Hemorrhagic Fever
• Chapter 6. Rift Valley Fever
• Chapter 7. Lujo Virus Hemorrhagic Fever
• Chapter 8. Toscana Virus Infection
• Chapter 9. Ebola Virus Disease
• Chapter 10. Crimean-Congo Hemorrhagic Fever
• Chapter 11. Phlebotomus Fever—Sandfly Fever
• Chapter 12. Chikungunya Fever
• Chapter 13. Nipah Virus Disease
• Chapter 14. Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) Infection
• Chapter 15. Human Bocavirus
• Chapter 16. Norovirus Gastroenteritis
• Chapter 17. Enterohemorrhagic Escherichia coli (EHEC): Hemorrhagic Colitis and Hemolytic Uremic Syndrome (HUS)
• Chapter 18. Emerging Clostridium difficile Infections
• Chapter 19. Multidrug-Resistant Tuberculosis
• Chapter 20. Acinetobacter Infections
• Chapter 21. Infections Due to NDM-1 Producers
• Chapter 22. The Exserohilum rostratum Incident: The Compounding Pharmacy as a Source of Emerging Infections
• Chapter 23. Mucormycosis
• Chapter 24. Lyme Borreliosis
• Chapter 25. Plasmodium knowlesi
• Chapter 26. Measles
• Chapter 27. Pertussis
• Chapter 28. Buruli Ulcer (Atypical Mycobacteria)
• Index